rs12921623

Positions:

• chr16-16002276-G-C
• chr16-16002276-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399410.8(ABCC1):​c.49-5540G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,902 control chromosomes in the GnomAD database, including 21,982 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21982 hom., cov: 32)
• Consequence: ABCC1 ENST00000399410.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.49-5540G>C		intron_variant		ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.49-5540G>C		intron_variant		1	NM_004996.4	ENSP00000382342	P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80575 AN: 151784 Hom.: 21984 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.540

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80600 AN: 151902 Hom.: 21982 Cov.: 32 AF XY: 0.524 AC XY: 38915 AN XY: 74222

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.534

Alfa AF: 0.439 Hom.: 1275

Bravo AF: 0.524

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.84
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12921623; hg19: chr16-16096133;